The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
A Duplex CRISPR-Cas9 Ribonucleoprotein Nanomedicine for Colorectal Cancer Gene Therapy
Abstract
Based on the high frequency of concurrent adenomatous polyposis coli ( APC ) and KRAS mutations and their strong cooperative interaction in human colorectal cancer (CRC) promotion, we herein develop a CRISPR-Cas9-based genome-editing nanomedicine to target both APC and KRAS mutations for the treatment of CRC. To this end, a hyaluronic acid (HA)-decorated phenylboronic dendrimer (HAPD) was designed for the targeted delivery of Cas9 ribonucleoprotein (RNP), by which both APC and KRAS genetic mutations harboring in CRC cells can be synergistically disrupted. Systemic administration of Cas9 RNP targeting APC and KRAS enabled by HAPD significantly inhibits tumor growth on xenografted and orthotopic CRC mouse models and also greatly prevents CRC-induced liver metastasis and lung metastasis. Thus, this duplex genome-editing system provides a promising gene therapy strategy for the treatment of human CRC and can be extended to other types of cancers with activated Wnt/β-catenin and RAS/extracellular signal-regulated kinase (ERK) pathways.
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Metadata
- Authors
- Wan, T., Pan, Q., Liu, C., Guo, J., Li, B., Yan, X., Cheng, Y., & Ping, Y.
- Affiliations
- Zhejiang University (CN)
- East China Normal University (CN)
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
- Corresponding author
- Cheng, Yiyun
- Venue
- Nano Letters
- Publisher
- American Chemical Society (ACS)
- Published
- 2021-11-12
- Volume
- 21
- Issue
- 22
- Pages
- 9761-9771
- ISSN
- 1530-6984 (ISSN-L)
- 1530-6992
- OpenAlex
- W3212753789
- Cited by
- 73
- References
- 40
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 22 · 2023: 22 · 2022: 11
- FWCI
- 3.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nano Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (82073779)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
- Keywords
- colorectal cancer, CRISPR/Cas9, APC mutation, KRAS mutation, hyaluronic acid, targeted delivery, genome editing, liver metastasis, lung metastasis, Wnt/β-catenin signaling, Ras/ERK pathway, gene therapy
- MeSH terms
- Animals, Ribonucleoproteins, Colorectal Neoplasms, Genetic Therapy, Nanomedicine, Mice, Wnt Signaling Pathway, CRISPR-Cas Systems
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